PDF(Pubmed)
Abstract：
Berberine bridge enzyme-like oxidases are often involved in natural product biosynthesis and are seen as essential enzymes for the generation of intricate pharmacophores. These oxidases have the ability to transfer a hydride atom to the FAD cofactor, which enables complex substrate modifications and rearrangements including (intramolecular) cyclizations, carbon-carbon bond formations, and nucleophilic additions. Despite the diverse range of activities, the mechanistic details of these reactions often remain incompletely understood. In this Review, we delve into the complexity that BBE-like oxidases from bacteria, fungal, and plant origins exhibit by providing an overview of the shared catalytic features and emphasizing the different reactivities. We propose four generalized modes of action by which BBE-like oxidases enable the synthesis of natural products, ranging from the classic alcohol oxidation reactions to less common amine and amide oxidation reactions. Exploring the mechanisms utilized by nature to produce its vast array of natural products is a subject of considerable interest and can lead to the discovery of unique biochemical activities.
摘要：
小檗碱桥酶样氧化酶通常参与天然产物的生物合成，被视为产生复杂药效团的必需酶。这些氧化酶具有将氢化物原子转移到FAD辅因子的能力，这使得复杂的底物修饰和重排，包括（分子内）环化，碳-碳键的形成，和亲核加成。尽管活动种类繁多,这些反应的机理细节往往还没有完全理解。在这篇评论中,我们深入研究了细菌中类似BBE的氧化酶的复杂性，真菌,和植物起源通过提供共同催化特征的概述并强调不同的反应性来展示。我们提出了四种广义的作用模式，通过这些模式，类BBE氧化酶可以合成天然产物，从经典的醇氧化反应到不太常见的胺和酰胺氧化反应。探索自然界用于生产其大量天然产物的机制是相当感兴趣的主题，并且可以导致发现独特的生化活性。
